Mechanism of oxidative stress in skeletal muscle atrophied by immobilization

Abstract

To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we measured the activities of antioxidant enzymes and xanthine oxidase (XOD) and carried out the cytochemical study of hydrogen peroxide in a typical slow red muscle, the soleus. Male Wistar rats (15 wk old), of which ankle joints of one hindlimb were immobilized in the fully extended position, were killed after 4, 8, or 12 days. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu-Zn-containing superoxide dismutase (Cu-Zn-SOD), Se-dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase, catalase, and glutathione reductase were measured spectrophotometrically. The XOD activity and the concentrations of hypoxanthine, xanthine, and urate were measured using a high-performance liquid chromatography. The cytochemical study of hydrogen peroxide in short-term organ culture was performed using an electron microscope. Increased Cu-Zn-SOD and decreased Mn-SOD in atrophy might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. The source of superoxide anions in the cytoplasm might be the increased superoxide-producing XOD. Enhanced generation of superoxide anions and increased Cu-Zn-SOD activity in atrophy suggested the enhanced generation of hydrogen peroxide in the cytoplasm. Due to the unchanged activity of Se-GSHPx and the unchanged or slightly increased activity of catalase in atrophy, the ability to degrade hydrogen peroxide might not increase so much. Hence, hydrogen peroxide is expected to be increased in atrophy. The cytochemical study supported this expectation.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Effects of Astaxanthin on Oxidative Key Enzyme and Capillarization in the Deep and Superficial Layers of Unloading-induced Atrophied Muscle

“…Some studies have reported that unloading causes oxidative stress such as overexpression of reactive oxygen species, leading to capillary regression in the atrophied muscle 15,16) . Although elevation of reactive oxygen species was not observed in the present study, the overexpression of reactive oxygen species has been shown in similarly atrophied muscles in other studies 4,5) , and in the present study, atrophied plantaris muscle may have been exposed to oxidative stress. Unsaturated fatty acids, a major component of mitochondrial membrane, are oxidized by reactive oxygen species 17) , and astaxanthin has been shown to inhibit lipid peroxidation 18) .…”

“…Muscle atrophy involves capillary regression, which is also more marked in oxidative muscle than in glycolic muscle 3) . It has been reported that inactivity results in overexpression of reactive oxygen species in atrophied muscle 4,5) , leading to capillary regression 6) .…”

From physical inactivity to immobilization: Dissecting the role of oxidative stress in skeletal muscle insulin resistance and atrophy

“…Mitochondria contributes to muscle ROS production during immobilization [52, [54][55][56], but other studies highlight that XO plays also an important role [57,58]. To the best of our knowledge no studies reported that NOX, NOS or ER plays a role in the production of ROS induced by immobilization.…”

Clinical definition and diagnostic criteria for sarcopenia

“…Thus, ATP is synthesized as necessary by myocyte mitochondria. Meanwhile, oxidative stress has been reported to increase in muscle tissue when activity is restricted, such as when immobilized in a cast or splint 40) . In sarcopenia, this is thought to increase the generation of active oxygen in mitochondria, which increases the damage to muscle tissue 41) .…”